KEGG   PATHWAY: hsa05140Help
Entry
hsa05140                    Pathway                                

Name
Leishmaniasis - Homo sapiens (human)
Description
Leishmania is an intracellular protozoan parasite of macrophages that causes visceral, mucosal, and cutaneous diseases. The parasite is transmitted to humans by sandflies, where they survive and proliferate intracellularly by deactivating the macrophage. Successful infection of Leishmania is achieved by alteration of signaling events in the host cell, leading to enhanced production of the autoinhibitory molecules like TGF-beta and decreased induction of cytokines such as IL12 for protective immunity. Nitric oxide production is also inhibited. In addition, defective expression of major histocompatibility complex (MHC) genes silences subsequent T cell activation mediated by macrophages, resulting in abnormal immune responses.
Class
Human Diseases; Infectious diseases
BRITE hierarchy
Pathway map
Leishmaniasis
hsa05140

All organismsOrtholog table
Disease
H00359  
Leishmaniasis
Organism
Homo sapiens (human) [GN:hsa]
Gene
7097  
TLR2; toll like receptor 2 [KO:K10159]
7099  
TLR4; toll like receptor 4 [KO:K10160]
4615  
MYD88; myeloid differentiation primary response 88 [KO:K04729]
3654  
IRAK1; interleukin 1 receptor associated kinase 1 [KO:K04730] [EC:2.7.11.1]
51135  
IRAK4; interleukin 1 receptor associated kinase 4 [KO:K04733] [EC:2.7.11.1]
7189  
TRAF6; TNF receptor associated factor 6 [KO:K03175] [EC:2.3.2.27]
6885  
MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
10454  
TAB1; TGF-beta activated kinase 1/MAP3K7 binding protein 1 [KO:K04403]
23118  
TAB2; TGF-beta activated kinase 1/MAP3K7 binding protein 2 [KO:K04404]
4793  
NFKBIB; NFKB inhibitor beta [KO:K02581]
4792  
NFKBIA; NFKB inhibitor alpha [KO:K04734]
4790  
NFKB1; nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 [KO:K02580]
5970  
RELA; v-rel avian reticuloendotheliosis viral oncogene homolog A [KO:K04735]
3552  
IL1A; interleukin 1 alpha [KO:K04383]
3553  
IL1B; interleukin 1 beta [KO:K04519]
3592  
IL12A; interleukin 12A [KO:K05406]
3593  
IL12B; interleukin 12B [KO:K05425]
7124  
TNF; tumor necrosis factor [KO:K03156]
3565  
IL4; interleukin 4 [KO:K05430]
4843  
NOS2; nitric oxide synthase 2 [KO:K13241] [EC:1.14.13.39]
3586  
IL10; interleukin 10 [KO:K05443]
7040  
TGFB1; transforming growth factor beta 1 [KO:K13375]
7042  
TGFB2; transforming growth factor beta 2 [KO:K13376]
7043  
TGFB3; transforming growth factor beta 3 [KO:K13377]
718  
C3; complement component 3 [KO:K03990]
1378  
CR1; complement component 3b/4b receptor 1 (Knops blood group) [KO:K04011]
3684  
ITGAM; integrin subunit alpha M [KO:K06461]
3689  
ITGB2; integrin subunit beta 2 [KO:K06464]
putative V-set and immunoglobulin domain-containing-like protein IGHV4OR15-8; K06856 immunoglobulin heavy chain [KO:K06856]
2209  
FCGR1A; Fc fragment of IgG receptor Ia [KO:K06498]
2212  
FCGR2A; Fc fragment of IgG receptor IIa [KO:K06472]
9103  
FCGR2C; Fc fragment of IgG receptor IIc (gene/pseudogene) [KO:K16824]
2214  
FCGR3A; Fc fragment of IgG receptor IIIa [KO:K06463]
2215  
FCGR3B; Fc fragment of IgG receptor IIIb [KO:K06463]
3676  
ITGA4; integrin subunit alpha 4 [KO:K06483]
3688  
ITGB1; integrin subunit beta 1 [KO:K05719]
5743  
PTGS2; prostaglandin-endoperoxide synthase 2 [KO:K11987] [EC:1.14.99.1]
5579  
PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
653361  
NCF1; neutrophil cytosolic factor 1 [KO:K08011]
4688  
NCF2; neutrophil cytosolic factor 2 [KO:K08010]
4689  
NCF4; neutrophil cytosolic factor 4 [KO:K08012]
1535  
CYBA; cytochrome b-245 alpha chain [KO:K08009]
5594  
MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  
MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
2002  
ELK1; ELK1, ETS transcription factor [KO:K04375]
2353  
FOS; FBJ murine osteosarcoma viral oncogene homolog [KO:K04379]
3725  
JUN; jun proto-oncogene [KO:K04448]
5600  
MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
6300  
MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
5603  
MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
1432  
MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
3458  
IFNG; interferon, gamma [KO:K04687]
3459  
IFNGR1; interferon gamma receptor 1 [KO:K05132]
3460  
IFNGR2; interferon gamma receptor 2 (interferon gamma transducer 1) [KO:K05133]
3716  
JAK1; Janus kinase 1 [KO:K11217] [EC:2.7.10.2]
3717  
JAK2; Janus kinase 2 [KO:K04447] [EC:2.7.10.2]
6772  
STAT1; signal transducer and activator of transcription 1 [KO:K11220]
3108  
HLA-DMA; major histocompatibility complex, class II, DM alpha [KO:K06752]
3109  
HLA-DMB; major histocompatibility complex, class II, DM beta [KO:K06752]
3111  
HLA-DOA; major histocompatibility complex, class II, DO alpha [KO:K06752]
3112  
HLA-DOB; major histocompatibility complex, class II, DO beta [KO:K06752]
3113  
HLA-DPA1; major histocompatibility complex, class II, DP alpha 1 [KO:K06752]
3115  
HLA-DPB1; major histocompatibility complex, class II, DP beta 1 [KO:K06752]
3117  
HLA-DQA1; major histocompatibility complex, class II, DQ alpha 1 [KO:K06752]
3118  
HLA-DQA2; major histocompatibility complex, class II, DQ alpha 2 [KO:K06752]
3119  
HLA-DQB1; major histocompatibility complex, class II, DQ beta 1 [KO:K06752]
3122  
HLA-DRA; major histocompatibility complex, class II, DR alpha [KO:K06752]
3123  
HLA-DRB1; major histocompatibility complex, class II, DR beta 1 [KO:K06752]
3125  
HLA-DRB3; major histocompatibility complex, class II, DR beta 3 [KO:K06752]
3126  
HLA-DRB4; major histocompatibility complex, class II, DR beta 4 [KO:K06752]
3127  
HLA-DRB5; major histocompatibility complex, class II, DR beta 5 [KO:K06752]
65108  
MARCKSL1; MARCKS-like 1 [KO:K13536]
5777  
PTPN6; protein tyrosine phosphatase, non-receptor type 6 [KO:K05697] [EC:3.1.3.48]
Compound
C00076  
Calcium cation
C00195  
N-Acylsphingosine
C00219  
Arachidonate
C00533  
Nitric oxide
C00584  
Prostaglandin E2
C02737  
Phosphatidylserine
Reference
  Authors
Cunningham AC
  Title
Parasitic adaptive mechanisms in infection by leishmania.
  Journal
Exp Mol Pathol 72:132-41 (2002)
Reference
  Authors
Nandan D, Knutson KL, Lo R, Reiner NE
  Title
Exploitation of host cell signaling machinery: activation of macrophage phosphotyrosine phosphatases as a novel mechanism of molecular microbial pathogenesis.
  Journal
J Leukoc Biol 67:464-70 (2000)
Reference
PMID:7591091
  Authors
Nandan D, Reiner NE
  Title
Attenuation of gamma interferon-induced tyrosine phosphorylation in mononuclear phagocytes infected with Leishmania donovani: selective inhibition of signaling through Janus kinases and Stat1.
  Journal
Infect Immun 63:4495-500 (1995)
Reference
  Authors
Nandan D, Lo R, Reiner NE
  Title
Activation of phosphotyrosine phosphatase activity attenuates mitogen-activated protein kinase signaling and inhibits c-FOS and nitric oxide synthase expression  in macrophages infected with Leishmania donovani.
  Journal
Infect Immun 67:4055-63 (1999)
Reference
PMID:7916951
  Authors
Reiner NE
  Title
Altered cell signaling and mononuclear phagocyte deactivation during intracellular infection.
  Journal
Immunol Today 15:374-81 (1994)
Reference
  Authors
Nandan D, Reiner NE
  Title
Leishmania donovani engages in regulatory interference by targeting macrophage protein tyrosine phosphatase SHP-1.
  Journal
Clin Immunol 114:266-77 (2005)
Reference
  Authors
Kima PE
  Title
The amastigote forms of Leishmania are experts at exploiting host cell processes  to establish infection and persist.
  Journal
Int J Parasitol 37:1087-96 (2007)
Reference
  Authors
Forget G, Gregory DJ, Olivier M
  Title
Proteasome-mediated degradation of STAT1alpha following infection of macrophages  with Leishmania donovani.
  Journal
J Biol Chem 280:30542-9 (2005)
Reference
  Authors
Cameron P, McGachy A, Anderson M, Paul A, Coombs GH, Mottram JC, Alexander J, Plevin R
  Title
Inhibition of lipopolysaccharide-induced macrophage IL-12 production by Leishmania mexicana amastigotes: the role of cysteine peptidases and the NF-kappaB signaling pathway.
  Journal
J Immunol 173:3297-304 (2004)
Reference
  Authors
Tuon FF, Amato VS, Bacha HA, Almusawi T, Duarte MI, Amato Neto V
  Title
Toll-like receptors and leishmaniasis.
  Journal
Infect Immun 76:866-72 (2008)
Reference
  Authors
Kropf P, Freudenberg N, Kalis C, Modolell M, Herath S, Galanos C, Freudenberg M, Muller I
  Title
Infection of C57BL/10ScCr and C57BL/10ScNCr mice with Leishmania major reveals a  role for Toll-like receptor 4 in the control of parasite replication.
  Journal
J Leukoc Biol 76:48-57 (2004)
Reference
  Authors
Feng GJ, Goodridge HS, Harnett MM, Wei XQ, Nikolaev AV, Higson AP, Liew FY
  Title
Extracellular signal-related kinase (ERK) and p38 mitogen-activated protein (MAP) kinases differentially regulate the lipopolysaccharide-mediated induction of inducible nitric oxide synthase and IL-12 in macrophages: Leishmania phosphoglycans subvert macrophage IL-12 production by targeting ERK MAP kinase.
  Journal
J Immunol 163:6403-12 (1999)
Reference
  Authors
Olivier M, Gregory DJ, Forget G
  Title
Subversion mechanisms by which Leishmania parasites can escape the host immune response: a signaling point of view.
  Journal
Clin Microbiol Rev 18:293-305 (2005)
Reference
  Authors
Matte C, Maion G, Mourad W, Olivier M
  Title
Leishmania donovani-induced macrophages cyclooxygenase-2 and prostaglandin E2 synthesis.
  Journal
Parasite Immunol 23:177-84 (2001)
Reference
  Authors
Ghosh S, Bhattacharyya S, Sirkar M, Sa GS, Das T, Majumdar D, Roy S, Majumdar S
  Title
Leishmania donovani suppresses activated protein 1 and NF-kappaB activation in host macrophages via ceramide generation: involvement of extracellular signal-regulated kinase.
  Journal
Infect Immun 70:6828-38 (2002)
Reference
PMID:9504340
  Authors
Bogdan C, Rollinghoff M
  Title
The immune response to Leishmania: mechanisms of parasite control and evasion.
  Journal
Int J Parasitol 28:121-34 (1998)
Reference
  Authors
Blanchette J, Abu-Dayyeh I, Hassani K, Whitcombe L, Olivier M
  Title
Regulation of macrophage nitric oxide production by the protein tyrosine phosphatase Src homology 2 domain phosphotyrosine phosphatase 1 (SHP-1).
  Journal
Immunology 127:123-33 (2009)
Reference
  Authors
Alexander J, Satoskar AR, Russell DG
  Title
Leishmania species: models of intracellular parasitism.
  Journal
J Cell Sci 112 Pt 18:2993-3002 (1999)
Reference
  Authors
Denkers EY, Butcher BA
  Title
Sabotage and exploitation in macrophages parasitized by intracellular protozoans.
  Journal
Trends Parasitol 21:35-41 (2005)
Reference
  Authors
Lodge R, Diallo TO, Descoteaux A
  Title
Leishmania donovani lipophosphoglycan blocks NADPH oxidase assembly at the phagosome membrane.
  Journal
Cell Microbiol 8:1922-31 (2006)
Reference
  Authors
de Freitas Balanco JM, Moreira ME, Bonomo A, Bozza PT, Amarante-Mendes G, Pirmez C, Barcinski MA
  Title
Apoptotic mimicry by an obligate intracellular parasite downregulates macrophage  microbicidal activity.
  Journal
Curr Biol 11:1870-3 (2001)
Reference
  Authors
Kane MM, Mosser DM
  Title
Leishmania parasites and their ploys to disrupt macrophage activation.
  Journal
Curr Opin Hematol 7:26-31 (2000)
Reference
  Authors
de Almeida MC, Vilhena V, Barral A, Barral-Netto M
  Title
Leishmanial infection: analysis of its first steps. A review.
  Journal
Mem Inst Oswaldo Cruz 98:861-70 (2003)
KO pathway
 

DBGET integrated database retrieval system